3Department of Clinical and Experimental Medicine, Section of Internal Medicine and Geriatrics,

Background. The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (a-tocopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability. Methods. The study sample included 827 older (65 years) persons (women, 54%) who participated in a population-based epidemiological study. Frail participants were identified based on the presence of at least three of five of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism. Results. Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend .015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertil